1OV4

Crystal structure of human DHEA-ST complexed with androsterone

Summary for 1OV4

• Entry DOI: 10.2210/pdb1ov4/pdb
• Related: 1EFH 1J99
• Descriptor: Alcohol sulfotransferase, SULFATE ION, (3Beta,5alpha)-3-Hydroxyandrostan-17-one, ... (4 entities in total)
• Functional Keywords: alpha/beta fold, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q06520
• Total number of polymer chains: 1
• Total formula weight: 35103.21

Authors

Chang, H.J.,Shi, R.,Rhese, P.,Lin, S.X. (deposition date: 2003-03-25, release date: 2004-02-17, Last modification date: 2023-08-16)

Primary citation

Chang, H.J.,Shi, R.,Rehse, P.,Lin, S.X.
Identifying androsterone (ADT) as a cognate substrate for human dehydroepiandrosterone sulfotransferase (DHEA-ST) important for steroid homeostasis: structure of the enzyme-ADT complex.
J.Biol.Chem., 279:2689-2696, 2004

PubMed Abstract: In steroid biosynthesis, human dehydroepiandrosterone sulfotransferase (DHEA-ST) in the adrenals has been reported to catalyze the transfer of the sulfonate group from 3'-phosphoadenosine-5'-phosphosulfate to dehydroepiandrosterone (DHEA). DHEA and its sulfate play roles as steroid precursors; however, the role of the enzyme in the catabolism of androgens is poorly understood. Androsterone sulfate is clinically recognized as one of the major androgen metabolites found in urine. Here it is demonstrated that this enzyme recognizes androsterone (ADT) as a cognate substrate with similar kinetics but a 2-fold specificity and stronger substrate inhibition than DHEA. The structure of human DHEA-ST in complex with ADT has been solved at 2.7 A resolution, confirming ADT recognition. Structural analysis has revealed the binding mode of ADT differs from that of DHEA, despite the similarity of the overall structure between the ADT and the DHEA binary complexes. Our results identify that this human enzyme is an ADT sulfotransferase as well as a DHEA sulfotransferase, implying an important role in steroid homeostasis for the adrenals and liver.

PubMed: 14573603
DOI: 10.1074/jbc.M310446200

Experimental method

X-RAY DIFFRACTION (2.7 Å)